Variant 3-31533134-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The NM_178862.3(STT3B):c.136G>A(p.Gly46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,302,234 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

STT3B
NM_178862.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

STT3B (HGNC:30611): (STT3 oligosaccharyltransferase complex catalytic subunit B) The protein encoded by this gene is a catalytic subunit of a protein complex that transfers oligosaccharides onto asparagine residues. Defects in this gene are a cause of congenital disorder of glycosylation Ix (CDG1X). [provided by RefSeq, Jun 2014]

STT3B links:

STT3B (HGNC:):

STT3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STT3B. . Gene score misZ 3.7557 (greater than the threshold 3.09). Trascript score misZ 3.2395 (greater than threshold 3.09). GenCC has associacion of gene with STT3B-congenital disorder of glycosylation.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049657524).

BP6

Variant 3-31533134-G-A is Benign according to our data. Variant chr3-31533134-G-A is described in ClinVar as [Benign]. Clinvar id is 702393.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STT3B	NM_178862.3 linkuse as main transcript	c.136G>A	p.Gly46Ser	missense_variant	1/16	ENST00000295770.4	NP_849193.1	Q8TCJ2
STT3B	XM_011533465.2 linkuse as main transcript	c.136G>A	p.Gly46Ser	missense_variant	1/10		XP_011531767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STT3B	ENST00000295770.4 linkuse as main transcript	c.136G>A	p.Gly46Ser	missense_variant	1/16	1	NM_178862.3	ENSP00000295770.2	Q8TCJ2
STT3B	ENST00000453168.5 linkuse as main transcript	n.497G>A		non_coding_transcript_exon_variant	1/10	1
STT3B	ENST00000423527.5 linkuse as main transcript	n.163G>A		non_coding_transcript_exon_variant	1/10	2

Frequencies

GnomAD3 genomes

AF:

0.000410

AC:

AN:

151268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000426

AC:

AN:

16424

Hom.:

AF XY:

0.000563

AC XY:

AN XY:

8888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0362

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000230

AC:

265

AN:

1150860

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

134

AN XY:

555700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00668

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.000610

GnomAD4 genome

AF:

0.000403

AC:

AN:

151374

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

AN XY:

73938

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0106

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000638

ExAC

AF:

0.00111

AC:

Asia WGS

AF:

0.00584

AC:

AN:

3440

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

STT3B-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

Eigen

Benign

-0.075

Eigen_PC

Benign

-0.026

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.060

REVEL

Benign

0.093

Sift

Benign

0.45

Sift4G

Benign

0.40

Polyphen

0.84

Vest4

0.19

MutPred

0.12

Loss of glycosylation at P51 (P = 0.0033);

MVP

0.22

MPC

0.84

ClinPred

0.14

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.13

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over